The chromatin-modifying protein HMGA2 promotes atypical teratoid/rhabdoid cell tumorigenicity

Harpreet Kaur, Marianne Hütt-Cabezas, Melanie F. Weingart, Jingying Xu, Yasumichi Kuwahara, Anat Erdreich-Epstein, Bernard E. Weissman, Charles G. Eberhart, Eric H. Raabe

Research output: Contribution to journalArticle

Abstract

Atypical teratoid/rhabdoid tumor (AT/RT) is an aggressive pediatric central nervous system tumor. The poor prognosis of AT/RT warrants identification of novel therapeutic targets and strategies. High-mobility Group AT-hook 2 (HMGA2) is a developmentally important chromatin-modifying protein that positively regulates tumor growth, self-renewal, and invasion in other cancer types. High-mobility group A2 was recently identified as being upregulated in AT/RT tissue, but the role of HMGA2 in brain tumors remains unknown. We used lentiviral short-hairpin RNA to suppress HMGA2 in AT/RT cell lines and found that loss of HMGA2 led to decreased cell growth, proliferation, and colony formation and increased apoptosis. We also found that suppression of HMGA2 negatively affected in vivo orthotopic xenograft tumor growth, more than doubling median survival of mice from 58 days to 153 days. Our results indicate a role for HMGA2 in AT/RT in vitro and in vivo and demonstrate that HMGA2 is a potential therapeutic target in these lethal pediatric tumors.

Original languageEnglish (US)
Pages (from-to)177-185
Number of pages9
JournalJournal of neuropathology and experimental neurology
Volume74
Issue number2
DOIs
StatePublished - Feb 2 2015

Keywords

  • Atypical teratoid/rhabdoid tumor
  • High-mobility group AT-hook 2
  • INI1
  • Malignant rhabdoid tumor
  • Pediatric brain tumor
  • SNF5.
  • let-7

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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